Impact of a single amino acid in the variable region 2 of the Old World monkey TRIM5α SPRY (B30.2) domain on anti-human immunodeficiency virus type 2 activity
Impact of a single amino acid in the variable region 2 of the Old World monkey TRIM5α SPRY (B30.2) domain on anti-human immunodeficiency virus type 2 activity
复制标题
DOI：
10.1016/j.virol.2009.03.004
复制
发表时间：
2009-05-25
期刊：
影响因子：
3.7
通讯作者：
Nakayama, Emi E.
中科院分区：
文献类型：
--
作者：
Kono, Ken;Bozek, Katarzyna;Nakayama, Emi E.
TRIM 5 α的SPRY结构域的可变区1（V1）是灵长类动物中物种特异性病毒限制的主要决定因素。我们先前报道了在食蟹猴TRIM 5 α的背景下含有嵌合TRIM 5 α的狒狒VI显示出有效的抗人类免疫缺陷病毒2型（HIV-2）活性。由于据报道狒狒对HIV-2感染敏感，因此狒狒TRIM 5 alpha V1限制HIV-2的能力与狒狒对HIV-2的敏感性之间存在差异。在这里介绍的研究中，我们研究了狒狒TRIM 5 α SPRY结构域的V2和V3在其抗HIV-2活性中的作用。含有整个狒狒SPRY结构域的嵌合TRIM 5 α显示出弱的抗HIV-2活性。这种活性的减弱是由狒狒TRIM 5 α V2中的单个丝氨酸到脯氨酸的取代引起的。这些发现表明，V1与SPRY的其他可变区的组合在灵长类动物TRIM 5 α的抗HIV-2活性中是重要的。(C)2009 Elsevier Inc. All rights reserved.
Variable region 1 (V1) of the SPRY domain of TRIM5 alpha is a major determinant for species-specific virus restriction in primates. We previously reported that a chimeric TRIM5 alpha containing baboon VI in the background of cynomolgus monkey TRIM5 alpha showed potent anti-human immunodeficiency virus type 2 (HIV-2) activity. Since baboons are reportedly sensitive to HIV-2 infection, there was a discrepancy between the ability of baboon TRIM5 alpha V1 to restrict HIV-2 and baboon sensitivity to HIV-2. In the study presented here, we examined the roles of V2 and V3 of the baboon TRIM5 alpha SPRY domain in its anti-HIV-2 activity. A chimeric TRIM5 alpha containing the entire baboon SPRY domain showed weak anti-HIV-2 activity. This attenuation Of activity Was caused by a single serine-to-proline substitution in baboon TRIM5 alpha V2. These findings indicate that the combination of V1 with other variable regions of SPRY is important in anti-HIV-2 activity of primate TRIM5 alpha. (C) 2009 Elsevier Inc. All rights reserved.